Fig. 4

PDXs and CDXs demonstrate differences in cell proliferation and immune response processes compared to patients. a Supervised hierarchical clustering of differentially regulated proteins (Two-tailed Student’s t-test, FDR < 0.05) in all patients compared to all PDXs. Heatmap depicts z-score normalized intensities for 94 proteins. Processes and pathways enriched in proteins in each of two distinct clusters are displayed (Fisher exact test, Benjamini-Hochberg FDR < 0.02). Enrichment test was performed using annotations for 5554 total proteins as background. Patient samples with reduced bone marrow disease involvement (blast count, B < 10%) are indicated. b-d Two-tailed paired Student’s t-test on (B) MKI67, (C) MCM2 and (D) PCNA protein abundance in 12 matched ALL patient and PDX pairs. Samples from the non-leukemic patient and from the two patients with blast infiltration less than 10% are highlighted in green and red respectively. Symbols * and ** denote p-values of 0.001 (MKI67), 0.03 (MCM2), and 0.006 (PCNA). e Proliferation rate of five matched primary and xenograft cells expanded in an ex vivo culture system. Experiment was performed in quintuplicates. f, g, h Proteins unique to either PDX or host, and found to be involved in established interactions and functional roles in (F) both B-ALL and T-ALL xenografts, (G) B-ALL patients, and (H) T-ALL patients (See methods for description of analysis in Metascape). i Schema for proteomics analysis on 380 cell line and 380 cell line-derived xenograft (CDX). Supervised hierarchical clustering of 321 proteins differentially regulated in cell lines (biological triplicates) and in liver and spleen from 380 CDX. Statistical analysis was performed with unpaired Student’s t-test, FDR < 0.05. j Biological processes enriched in proteins markedly abundant in 380 CDX (green cluster) and processes deficient in 380 CDX (red cluster). k, l The abundance of protein receptors involved in immune regulation is markedly different in 380 cell line and CDX